DE2806030C2 - Process for the production of a tubular blood vessel prosthesis - Google Patents

Description

ίο The invention relates to a method for producing a tubular blood vessel prosthesis according to the preambles of claims 1 and 2.

Such a method is known from DE-OS 25 34 935. A fiber mat material, in particular in the form of a prosthetic device such. B. a prosthetic blood vessel is described by electrostatic Spinning an organic material into fibers and by taking these fibers into or onto them a suitable collection device has been made.

The process requires constant generation and maintenance of an electric field of 5 to 1000 kV. Not only is a generator necessary for this, but the whole process is influenced by it. So the starting material must have a certain conductivity; it must be the best possible distance from the nozzle of the charged curses experimentally in dependence wedge of?. B. the level of electrostatic charge, the dimension of the nozzle, the flow rate, the electrically charged surfaces are determined; Everyone Load-bearing parts, bearings and all other components of the system must be adequately insulated. It becomes a fleece mat obtain. The fiber direction is constant. It is determined by the electrostatic field lines. Of the Any additional air stream used serves to accelerate the curing, but can also be used for Deposition of the fibers in the same location and direction can be used. Eventually there will be vascular prostheses obtained, which is usually a reinforcement z. B. need by spirals or woven textiles. Through this

■ to its elasticity is lost world-wide.

Another method of making vascular prostheses and implants in the form of tubes and hoses is described in DE-OS 20 25 358. It will be short. 10 to 15 μm thick polyester fibers accordingly the papermaking technology irregularly deposited into a fiber fleece and then adhesive or connected to one another by melting the fiber surface. The sheet-like nonwoven fabric then becomes rolled up a pipe. By gluing the long edges with a suitable adhesive, the claimed vascular prolheses received. The disadvantage of this process is that as an intermediate inelastic two-dimensional planar structure will. The consequence of this is that you don’t have to worry about the elasticity and shape of the food product can make high demands.

In DE-OS 19 12 627 it is taught to manufacture a fabric tube by interweaving continuous filaments made of collagen that have been produced by extrusion. The preparation of this biological base material and the production of the threads is relatively complex and also not unproblematic. The threads have to go through a lengthy refining process before they can be processed further. The fabric is made from prefabricated continuous threads. Due to the weave structure of the fabric, the threads run at a crossing angle of 90 ⁼ . This crossing angle is fixed in terms of binding technology and machine technology.

placed and cannot be varied. The preferred direction of the continuous filaments is therefore determined in two directions, which cross at an angle of 90 °. The alignment of the threads cannot therefore be varied.

DE-OS 25 08 570, DE-OS 25 14 231 and DE-OS 27 02 513 describe processes for the production of Microporous, tubular prostheses made of polytetrafluoroethylene using the so-called paste extrusion process. The radial expansion process carried out after the sintering process results in fibrils, which together with the nodes represent the microporous structure. The fibrils are relatively uniform Length and go at their ends in a chopstick structure. Such prostheses have a relatively good one Kink stability on, without additional pleating, but the wall is almost not elastic. Even Such prostheses are due to their chemical and biological inertness and the smoothness of the surface not firmly surrounded by connective tissue in the body, which can lead to long-term problems. Also has Polytetrafluoroethylene has poor creep resistance. The knot-fibril structure is created by the twisting process. As a result, the nodes or fibrils are aligned in two directions, which are mutually exclusive cross at an angle of approx. 90 °. The angle of intersection is process-specific and not determined variable. Due to the process steps, extrusion into a tube and its stretching in In the longitudinal direction, only prostheses with a simple geometric shape are possible.

It is the object of the invention. a simplified and extremely variable method of manufacture to provide tubular blood vessel prostheses made of several fiber layers if necessary, at In particular, everything that has to do with electrostatic spinning, directly or indirectly, is omitted. In addition, the new method should lead to blood vessel prostheses with better properties, in particular in terms of elasticity and strength.

According to the invention, this object is achieved by what is stated in the characterizing parts of claims 1 or 2 specified process steps solved.

The method according to the invention leads to a blood vessel prehesis, which i.a. can be bent elastically to relatively small radii of curvature without the risk of kinking can and which is radially elastically expandable. so that such a blood vessel prosthesis through after implantation the fluctuating or pulsating blood pressure is reversibly widened and narrowed again, a property which also have the natural arteries and veins.

It is particularly beneficial to ensure that the radial expandability is permanent after implantation by by making the hose consisting of the individual fibers in such a way that its cavities are made up of the individual fibers resulting hose are to be achieved.

The outer surface of the blood vessel prosthesis can mostly are advantageously left in the rough shape resulting from the manufacture of individual fibers, since this is a desirable surface finish of the artificial blood vessel prosthesis, at least in many cases corresponds to the safe, rapid growth of connective tissue to the blood vessel prosthesis after it Implantation ensures the position of this, forming a section of an artery or vein. prosthesis fixed.

However, there may also be cases where it is desirable if the blood vessel prosthesis has an almost smooth surface Has. This can optionally be done by making fine, thin fibers for the outer layer or by suitable post-treatment, for example by calendering the outer surface of the prosthesis, likewise without Difficulty reaching.

It is also possible with the procedure. Solutions of polymer mixtures, block polymers, or others To spray polymers whose biological behavior is known to the extent that only a little connective tissue in the to prosthetic structure grows in, but rather only connective tissue adheres to the outer surface of the prosthesis. Likewise, the inner surface of the prosthesis can according to the process according to the invention can be left with the roughness caused by the individual fibers or a other suitable condition, which means different Way can be achieved. In a preferred embodiment it can be provided that at the manufacture of the prosthesis, the individual fibers on a seamless tube located on the rod made of flexible Foil, preferably elastic plastic film, are applied, which is an inner tube of the finished Forms blood vessel prosthesis, and, since it consists of foil, optionally a completely smooth inner surface the prosthesis can form. This too can. preferably producible by the method according to claim 4, If necessary, however, the inner film tube applied to the rod as a finished tube is also impermeable to liquid be, or only for certain blood components, such as enzymes, be permeable. Even Μ This inner tube can be impermeable to connective tissue and so prevent it from growing into the lumen of the prosthesis through its wall can.

With the process can be different shapes

^J > the tubular prostheses are made. So it can be cylindrical, for example, square-cylindrical, or non-cylindrical. Their cross-sections can be round.

oval, elliptical or the like.

You can choose their diameter and / or their cross-sectional shape also vary over their length, be it continuously changing, gradually or the like. Hence let it In addition to blood vessel prostheses, they also have other tubular organ prostheses, such as 13. Esophagus, trachea, ureter, Manufacture urethral, ductal, intestinal or lymphatic prostheses. It is also possible to use nerve splints or to produce arterial-venous shunts as they are used in dialysis patients.

Blood vessel prostheses produced according to the novel process can, if desired, be post-treated ^{5 (1} , for example to make them hydrophilic or hydrophobic or negatively charged, depending on the desired interface properties of the prosthesis. The following treatments of the inner surface of the prosthesis, individually or In suitable combinations, in question:

a) Grafting by adding a radical initiator In the polymer.

b) Irradiation of the surface, thereby chemical conversion in the polymer.

c) Irradiation of the surface in the presence of a monomer under the action of protective gas.

d) Incorporation of another polymer particle in the polymer surface, which in turn has the desired and have the necessary interface properties with respect to the blood and its components and thus characterize the surface of the original polymer obtained in this way.

The production of the individual fibers can be done in different ways Way to be done. In a preferred embodiment of this method according to the invention all fibers or at least a considerable number of the fibers produced by fiber spraying, d. H. that a polymer solution is sprayed from a spray or atomizer nozzle with pressure, which then Solution immediately after escaping into the air form fibers with different lungs and thickness, which fibers then by the spray pressure itself or by an additional air flow, preferably by compressed air can be formed, which flows out together with the polymer solution from the same nozzle opening to the Rod can be transposed. Depending on the air flow, not all fibers reach the rod. The lost fibers can be redissolved and the solution used again.

It can also be beneficial if the solution is through the nozzle is sprayed in a liquid medium with the supply of compressed air with the formation of additional fibers will. For example, water or inorganic or organic solvents can be used as the liquid medium can be used in which the polymer used does not dissolve, but precipitates. The fibers will in this case transported by the flow of the solution to a rod rotating within the flow of the solution and attached to form a fleece with the formation of a fiber bar.

It is particularly advantageous if all the individual fibers of the blood vessel prosthesis in question are sprayed through fibers be generated. This is because fiber spraying leads to fibers that are tacky immediately after their production Have surface which can remain sticky without difficulty until it is wound onto the rod are. If, on the other hand, what can be possible and often expedient in many cases, is provided, that the individual fibers by dissolving a sliver, for example one produced on a stretch Sliver, wins and pneumatically transported to the rod, then they have to during their flight to the The rod can be sprayed with solvent or binder to make its surface sticky, unless that these fibers are used in addition to fibers obtained by fiber spraying and by those produced by the spray method sticky fibers are stuck together.

Individual fibers made of polyurethane have proven to be particularly advantageous. Their elasticity leads to blood vessel prostheses, which have particularly favorable radial elastic properties, as tests have shown. It can however, other fibers made of polymeric plastics can also be used, if this is expedient on a case-by-case basis is, preferably made of thermoplastics.

The winding up of the individual fibers on the rod to form the hose or jacket formed by them can alone done by turning the rod. However, it is also conceivable that this winding up by a to the Rod can cause circulating air flow, which is an axial component extending in the axial direction of the rod can have, d. that is, can flow around the rod in a spiral or helical manner. If necessary, a such circulating air flow can also be combined with a rotation of the rod. It is also conceivable that in the case of fibers produced in the spray process, the polymer solution spraying spray or atomizer nozzle rotates around the rod.

Although in many cases just one is sufficient Using some sort of single fiber of the same staple diagram can, if desired, use the mean length and / or mean thickness of the individual fibers during the manufacture of the blood vessel prosthesis through modification the liquid pressure and / or the compressed air pressure and / or by using a different solvent mixture can be varied. It can also be advantageous to use individual fibers made from other polymers, copolymers or to produce polymer mixtures by spraying fibers and to incorporate them in the fiber fleece. this can be achieved that from a further nozzle at least temporarily one of the individual fibers, such as explained above, have a certain preferred direction in each layer 25 ', 25 ". These two preferred directions are different and can preferably cross each other.

When blood vessel prostheses with multiple layers of fibers, such as, for example, the fiber layers 25 'and 25 "are produced, the method can be optionally used meet so that adjacent layers are glued together or not. In the latter case, one includes Layer the layer located within it only loosely, but these layers are due to the roughness of the Adjacent layer surfaces are prevented from axially shifting against one another. A sticking Adjacent layers can be reached in a simple manner if, at the transition from one Layer to next layer does not allow the outer surface of the first layer to dry, d. H., either during the angular adjustment of the rod 19 continues with the fiber spraying or the fiber spraying interrupts only so briefly and thereby sets the rod 19 in the new angular position that the surface of the The first layer produced is still sticky when the first fibers intended for the next layer arrive. If, on the other hand, the fiber spraying is interrupted after a layer has been produced, until the outer surface is visible this layer has dried, and only then does the production of the next layer begin In the above-described embodiments, there is no adhesive bond between the two layers, although the fibers of the second layer got sticky to the first layer.

In Figure 1, L denotes the distance between the nozzle 10 and the point 20. The rod 19 can be made of metal or other material. It can preferably consist of a plastic so that it can be removed from its interior after the production of the prosthesis 23 by dissolving it, thereby avoiding any risk of damage to the prosthesis.

The following is the production of an artificial artery or vein 23 on the rod 19 of this embodiment described in more detail.

In this embodiment, the resulting downstream of the atomizer nozzle 10, single fibers that are still sticky are blown to the rod 19 solely by the compressed air flowing out of the annular gap 16, so that no other air is required for the pneumatic transport of these fibers to the rod. Of course not all fibers get to the rod. The fibers passing laterally on the rod 19 can be caught and put back into solution.

The following is also the case with this manufacturing process: The fibers manufactured using the spray process have different lengths. and different titer.

Their fineness and their stacking diagram can be varied by the pressure with which they come out of the cannula

18 or by the negative pressure generated by compressed air or by an overpressure generated inside the storage container 17 containing the polymer solution and also by the type of polymer solution and the relative amount of the polymer solution flowing out of the cannula. The viscosity of the polymer solution can always be set differently by different percentage amounts of solvent, and this also allows both the sticky properties of the fibers and their length, etc., to be varied. The elasticity of the individual fibers depends on the polymer plastic used. As mentioned, polyurethane solutions can preferably be provided as polymer solutions.

With the device shown in Fig. 1, the tube 25 consisting of the individual fibers (which is not the outer tube of the blood vessel prosthesis 23 if the inner film tube 24 is present, but the inner film tube 24 can also be omitted) can be produced in such a way that they produced by the fiber spraying sticky individual fibers, which are pneumatically transported to the rod 19 by the air flow generated from the annular gap 16 of the nozzle 10, on at least one side of the outer circumference of the artificial fiber tube 25 being manufactured, a tuft 28, the The speed of rotation of the rod 19 about its longitudinal axis is such that the length of this tuft 28 assumes a stationary mean value which can correspond approximately to the length of the longest individual fibers. The newly arriving individual fibers adhere to the tuft 28 due to their sticky surface. The tuft 28, viewed from the atomizer nozzle 10, extends to one or both of the longitudinal cables of the rod 19 in the direction away from the atomizer nozzle 10 and, by the rotation of the rod 19 around its longitudinal axis in a direction of rotation C, is continuously on the circumference of the Rod 19 wound. The base of the tuft begins approximately at the surface line 29 or 29 'of the respective outer circumference of the blood vessel prosthesis being manufactured. Depending on the process conditions, one tuft 28 (Fig. 3) is formed on a surface line 29 or two tufts 28 (Fig. 4) on two approximately diametrically opposite surface lines 29 and 29 ', which are approximately the surface lines at which each the air flow B separates from the respective hose circumference. In Fig. 3 and Fig. 4, C indicates the direction of rotation. The speed of the rod 19 is, however, such that, as mentioned, the tuft 28 is always present, so that the newly arriving individual fibers are "glued " to this tuft, lengthening its open end. At the same speed at which this tuft 28 wlTd extended by newly arriving fibers, it is wound onto the rod 19, so that a stationary length of the tuft 28 results. The newly arriving fibers are therefore attached to the tuft in a similar way to the open-end spinning process, lengthening its open end. However, these individual fibers are not twisted together into a yarn, but are oriented in the direction of this air flow B by the air flow generated by the compressed air flowing out of the atomizer nozzle 10, which has the direction according to the arrows B on the rod 19 and so with this preferred direction on the Rod 19 wound. If the angle α is smaller than + 90 ° and -90 ° and larger than 0 °; there is a helical winding up

of the fibers of the tuft 28 on the rod 19. Depending on their length, the fibers extend around the rod 19 at an angle smaller than 360 ° or at an angle corresponding to or greater than 360 °. In the case of fiber atomization, both fibers can arise that can only be wound less than 360 ° around the rod, as well as fibers that can be wound more than 360 ° around the rod. The the fiber tuft 28 forming individual fibers are not aligned precisely parallel to each other, but have only a preferential direction to the air flow B. Depending on the addition of these individual fibers of the beard 28 also individualized fibers may be parallel transversely extend partly to the air flow B. In any case, however, there is a preferred direction of the fibers in the tuft 28 and thus also in the hose 25 produced from individual fibers, this preferred direction, as mentioned, can be changed continuously or discontinuously by changing the angle α between +90 and -90 " It is usually particularly advantageous to form several layers 25 'and 25 "(Fig. 2), which have preferred directions of their individual fibers that cross each other. Of course, more than two such layers can also be formed.
The device shown in Fig. I thus enables an extraordinarily large variability of blood vessel prostheses to be produced, as was previously not possible.

Execution examples c

Below are some specific creation examples described which were carried out millels of the device shown in Fig. I.

In the following production examples, the following physical quantities were uniform:

Distance L = 1.5 m,

as atomizer nozzle 10, one from Lechler, Stuttgart, Pneumatic atomizer nozzle sold under the type designation DRS 142.

The compressed air pressure at the inlet of the atomizer nozzle 1 (1 was 2.5 bar. The result was that the compressed air was salted out through the atomizer nozzle 10 of 16 NmVh (standard cubic meters / h). A constant overpressure of 3 bar was constantly maintained in the storage container 17, whichever the polymer solution in it is polluted.

The speed of rotation of the rod 19 about its longitudinal axis was 20 to 50 rpm.

Execution example 1

A circular slab 19 made of polyvinyl alcohol was used as the rod 19 with 4 mm outer diameter used. An artificial blood vessel prolapse was created on him Spraying a polyurethane solution, made up according to recipe 1, produced, so only from each other glued individual fibers.

The sprayed amount of polyurethane solution was 200 g and the spraying time was 17 minutes.

A tube made of two layers was produced as a blood vessel prosthesis, the rod 19 rotating continuously during the production of the individual layer and being set at a certain angle α in each case:

1st layer: = +60 " Angle a = 0.45 mm Layer thickness 2 layer: = -60 ° Angle a = 0.45 mm Layer thickness

The wall thickness of the blood vessel prosthesis was 0.9 mm.

After five minutes of internal drying at 22 ° C on the stick 19 the blood vessel prosthesis was pushed off the rod 19 and stored hanging for further drying.

The inner surface of the resulting blood vessel prosthesis was lasrlg rough, the wall porous. The outside surface w; t also fibrous rough.

Embodiment 2

A cylindrical tube made of polyvinyl alcohol with an aulia diameter of 6 mm was used as the rod 19 and a wall thickness of 1 mm on a circular cylindrical steel rod with an outer diameter of 4 mm was raised, used.

An inner film tube was applied to this. The polymer solution used for this was according to the recipe 2 has been produced. The thickness of the inner film tube produced was 0.07 mm. A polymer solution according to recipe 3 was used for fiber spraying.

The sprayed amount of polymer solution was 200 g, the spraying time was 12 min. Ls were again in short periods of time Distances with rotation of the rod 19 made two fiber layers, in which the fibers are different Cut preferred directions.

1 layer: = +45 ' Angle a = 0.35 mm Layer thickness = 100 g amount of polishing solution consumed 2 layer: = -45 ^l Angle a = 0.35 mm Layer thickness = 100 g spent polynic solution mentiC

The two layers hold different fiber densities, with the first layer having the higher fiber density had, the second layer the lower.

This was made possible by higher / urgent throughput (setting by means of the needle 18 '. Fig. 1) on polymer solution through uie nozzle 10 during the production of the 1 layer 25 ' compared to that achieved in the 2nd layer 25 ".

After the slight drying of the blistering prosthesis on the rod at room temperature (22 C), the Geläßproihese could be pushed off the rod and became stored hanging for further drying. These from the film tube and the reading connected to it, The artificial blood vessel prolhesis consisting of a two-layer fibrous moth tube had a smooth inner surface and a fibrous, rough outer surface. Your inner film tube prevents connective tissue from growing. However, the connective tissue can pass through the 1st layer grow in up to the 2nd layer, whereby this prosthesis in its position in the body in which it is implanted is fixed.

Embodiment 3

A steel rod 19 was used, the diameter of which was 4 mm.

A commercially available, seamlessly manufactured by the screw extrusion process was used as the inner film tube Foil tube was used, which consisted of the same basic substance as used to manufacture the Recipe 4 was used. The wall thickness of the film tube was 0.1 mm. The ones for fiber spraying The polymer solution used was made up according to recipe 4, the sprayed amount was 275 g, there were two Fiber layers made with the same fiber density.

1st layer:
Angle a
Layer thickness

2 layer:
Angle a
Layer thickness

= + 50 °
= 0.5 mm

= -60 °
= 0.5 mm

Spray duration: 12 min

Total layer thickness: 1.1 mm

The finished prosthesis was pushed off the rod 19 and stored hanging to dry at room temperature. An artificial blood vessel prosthesis with a very smooth inner surface was created. The outside surface was rough and not porous.

Recipes used:
Recipe 1

The starting product was an aromatic polyether urethane in granular form, manufactured by B. F. Goodrich, Holland, under the name ESTANL 5714 Fl Resin.

Properties of the polyurethane according to the manufacturer's information:

Specific weight 1.11 g / cm tensile strenght 3M) 0 N / cm Elongation at break 560% Shore hardness A 80

10 parts of these granules were dissolved in 14 parts acetone and 10 parts of n.n-Diniethyllonnamiii dissolved.

Recipe 2

The starting product used was an aliphatic polyester urethane which was manufactured and sold in dissolved form by Bayer AG, Leverkusen, under the type designation "Impranil ELH".
Properties of the material according to the manufacturer's information:

Solution viscosity 350 poise (25 C)

Movie properties:

_4th Shore hardness A 88

Tensile strength: 5200 N / cm ^:

Elongation at break: 420%

Delivery form (according to the manufacturer's information):
Impranil ELH solution in xylene / isopropanol / ethylglycol = 29: 20: 21. Approx. 3 (kig.

40 parts of this solution were mixed with 5 parts of isopropanol, 40 parts of toluene and 15 parts of n.n-dimethylformamide diluted.

Recipe 3

The starting product is identical to that of recipe 2: 30% solution of an aliphatic polyurethane, manufactured by Bayer AG, Leverkusen. 200 parts of this solution were mixed with 25 parts of acetone, 150 Parts of toluene and 20 parts of isopropanol diluted.

Recipe 4

The basic substance is a polyether urethane in granules 5 form made by UPJOHN, USA. under the type designation »Pellethane CPR 2363 - 80 A Urethane Elastoplastic Rolymer «is manufactured and sold.

Properties of this polyether urine according to information of the manufacturer:

Specific weight: 1.13 g / cm 'Tensile strength: 4200 N / cnr

Elongation at break: 550%

400 parts of these granules were dissolved in 650 parts of acetone, 70 parts of isopropanol and 300 parts of n.n-dimethylformamide solved.

For this purpose 3 sheets of drawings

Claims (10)

Patent claims: 1. Process for the production of a tubular Blood vessel prosthesis by producing individual fibers by spraying a solution of a polymer through a nozzle, these individual fibers are transported to a rod and the individual fibers are wound up the rod, characterized in that the solution through the nozzle into a gaseous or liquid Medium arranged in front of the nozzle is sprayed into individual fibers with the supply of compressed air and the individual fibers are transported to and around the rod by the resulting flow in the medium its longitudinal axis rotating rod directed downstream a fiber fleece in the form of tufts arises and is wound up. 2. Process for the production of a tubular blood vessel prosthesis by producing individual fibers by spraying a solution of a polymer through a nozzle. Transport of these individual fibers into a rod and winding the individual fibers onto the rod, characterized in that the solution through the nozzle into a gaseous or liquid medium arranged in front of the nozzle with the supply of Compressed air is sprayed into finned fibers and the liinzelfascm by the resulting flow in the Medium transported to the rod and directed downstream on the rod a fiber fleece in the form of Faserbärlen is created, which is wound up by a flow of the medium circulating around the rod will. 3. The method according to claim 1 or 2, characterized in that the individual fibers with one another stick to the rod due to their still sticky surfaces. 4. The method according to claim 1 or 2, characterized in that the obtained by fiber spraying Individual fibers are added to the stick at the latest when they are attached to the rod obtained by mechanical dissolution of a fiber structure and then pneumatically to the rod or in the flow of those obtained by spraying with a hair dryer Fibers are brought and transported to the rod. 5. The method according to claim 4, characterized in that the obtained by mechanical dissolution Individual fibers are glued to one another on the rod by means of additionally introduced liquid adhesive will. 6. The method according to any one of claims 1 to 5, characterized in that the rod during the Accumulation of the finned fibers inclined, at least at times, at an angle to the direction of arrival of these fibers will. 7. The method according to any one of claims 1 to 5, characterized in that to change the fiber preference orientation The inclination of the nozzle is changed. 8. The method according to claim 6, characterized in that the inclination of the rod relative to Arrival rate of fibers is changed. 9. The method according to any one of claims 5 or 6, characterized in that after production of a Fiber layer of the hose interrupted the supply of fibers and then added another layer changed fiber preferred orientation direction is applied. 10. The method according to any one of claims 1, 3 to 9, characterized in that the rod at least is temporarily rotated around its longitudinal axis at a constant rotational speed.